The overall approach used to study the metabolic regulation of growth and body composition is essentially one of using among and within specie variations to exaggerate metabolic parameters. In the first phase of the experimental design, we are attempting to identify key tissue, cellular and molecular differences which permit wide variations in body composition. The second phase involves the manipulation of diet, endocrine activity and physical activity to control body composition and cellular development. The procedures used to characterize metabolic profiles will involve the following: the measurement of enzyme levels in liver, adipose and muscle tissues; the determination of substrate utilization by isolated cells and tissue slices; and the identification of metabolite and hormone patterns in blood plasma. These observations will be performed during the onset of hyperlipogenesis so that the primary events associated with changes in body composition may be identified. Key rate limiting enzymes will be selected for measurement from major pathways of lipogenesis, gluconeogenesis, glycolysis and amino acid catabolism. Techniques for enzyme and metabolite measurements have been perfected and are established procedures in our laboratories.